- Phase 3 trials of DOR/ISL showed minimal changes in weight and lipids in HIV-1 patients.
- FDA set a target action date of April 28, 2026, for the DOR/ISL New Drug Application.
- DOR/ISL maintained viral suppression and showed non-inferiority to BIC/FTC/TAF.
- No treatment-emergent resistance observed in DOR/ISL trials.
Trial Overview
Merck presented data from Phase 3 trials evaluating the investigational once-daily oral two-drug regimen of doravirine/islatravir (DOR/ISL) in adults with HIV-1 infection. The trials focused on patients who were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) or baseline antiretroviral therapy (bART).
Key Findings
The trials showed minimal changes in weight and body composition at Week 48 for those who switched to DOR/ISL from BIC/FTC/TAF, comparable to those who continued their original regimen. No clinically meaningful changes were observed in fasting lipids or insulin resistance across the trials.
Regulatory Status
The U.S. FDA has accepted the New Drug Application for DOR/ISL, with a target action date set for April 28, 2026, under the Prescription Drug User Fee Act (PDUFA).
Safety and Efficacy
DOR/ISL maintained viral suppression and demonstrated non-inferiority to the three-drug regimen BIC/FTC/TAF, with no observed treatment-emergent resistance. Adverse events and discontinuations due to drug-related adverse events were similar between DOR/ISL and comparator groups.
Additional Insights
In the double-blind trial MK-8591A-052, mean changes in weight and body composition were minimal and similar between treatment groups. Across both trials, changes in fasting lipids and insulin resistance were minimal, with a comparable proportion of participants initiating lipid-lowering therapy.
